EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro

Jang, Minsu; Park, Rackhyun; Park, Yea-In; Cha, Yeo-Eun; Yamamoto, Ayane; Lee, Jin I.; Park, Junsoo

doi:10.1016/j.bbrc.2021.02.016

Cited by 80 publications

(83 citation statements)

References 16 publications

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“…In addition, among the catechins, EGCG was the strongest inhibitor of live human coronavirus (HCoV OC43) infection (Fig. 4 d, e), which agrees with a recent report that EGCG treatment decreased the levels of HCoV OC43 viral RNA and protein in infected cell media through inhibition of 3CL-protease activity of the virus [ 45 ]. These data provide the direct evidence to support the assumption that high green tea consumption was associated with low morbidity and mortality of COVID-19 at the level of individual countries [ 12 ].…”

Section: Discussionsupporting

confidence: 90%

Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

et al. 2021

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Background As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Results We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. Conclusions These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

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Section: Discussionsupporting

confidence: 90%

Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

et al. 2021

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“…Following PL pro -UbV complex formation, PL pro deubiquitylation, deISGylation and protease activities were significantly hindered and viral progeny were much less infectious [98]. Smallmolecule inhibitor screens have subsequently identified the substrate-binding pocket and the ISG15 binding site of PL pro as important determinants of viral fitness and could serve as attractive targets for antiviral drug development [136][137][138][139][140][141][142]. For example, the small molecule GRL0617 is one of the most promising SARS-CoV-2 inhibitors currently being studied that sterically blocks the binding of ISG15 and ubiquitin to PL pro [137,142].…”

Section: Viral Antagonism Of Herc5 and Isgylationmentioning

confidence: 99%

HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response

Mathieu

Paparisto

Barr

et al. 2021

Viruses

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Mammalian cells have developed an elaborate network of immunoproteins that serve to identify and combat viral pathogens. Interferon-stimulated gene 15 (ISG15) is a 15.2 kDa tandem ubiquitin-like protein (UBL) that is used by specific E1–E2–E3 ubiquitin cascade enzymes to interfere with the activity of viral proteins. Recent biochemical studies have demonstrated how the E3 ligase HECT and RCC1-containing protein 5 (HERC5) regulates ISG15 signaling in response to hepatitis C (HCV), influenza-A (IAV), human immunodeficiency virus (HIV), SARS-CoV-2 and other viral infections. Taken together, the potent antiviral activity displayed by HERC5 and ISG15 make them promising drug targets for the development of novel antiviral therapeutics that can augment the host antiviral response. In this review, we examine the emerging role of ISG15 in antiviral immunity with a particular focus on how HERC5 orchestrates the specific and timely ISGylation of viral proteins in response to infection.

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“…Additionally, in our experiments, EGCG was preincubated with SARS-CoV-2 before infection of cells, ruling out its effects on non-structural proteins. EGCG was recently demonstrated to inhibit SARS-CoV-2 3CL-protease and coronavirus replication by inhibition of 3CL protease [35] , suggesting the all-round inhibitory potency of EGCG on SARS-CoV-2. Notably, we also observed that EGCG could inhibit the infection of 4 kinds of mutant S-pseudotyped lentivirus in human ACE2 overexpressing cells, indicating that ECGC has a good prevention prospect for the mutated SARS-COV-2.…”

Section: Discussionmentioning

confidence: 99%

Identification of natural compounds as SARS-CoV-2 entry inhibitors by molecular docking-based virtual screening with bio-layer interferometry

Zhang

Hamdoun

Chen

et al. 2021

Pharmacological Research

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Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100 μM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.

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EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro

Cited by 80 publications

References 16 publications

Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response

Identification of natural compounds as SARS-CoV-2 entry inhibitors by molecular docking-based virtual screening with bio-layer interferometry

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